KR100710958B1 - 데하이드로 아미노산 - Google Patents
데하이드로 아미노산 Download PDFInfo
- Publication number
- KR100710958B1 KR100710958B1 KR1020027010215A KR20027010215A KR100710958B1 KR 100710958 B1 KR100710958 B1 KR 100710958B1 KR 1020027010215 A KR1020027010215 A KR 1020027010215A KR 20027010215 A KR20027010215 A KR 20027010215A KR 100710958 B1 KR100710958 B1 KR 100710958B1
- Authority
- KR
- South Korea
- Prior art keywords
- amino
- hydrogen
- formula
- compound
- acid
- Prior art date
Links
- 239000002253 acid Substances 0.000 title description 31
- 150000007513 acids Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 498
- 239000001257 hydrogen Substances 0.000 claims description 244
- 229910052739 hydrogen Inorganic materials 0.000 claims description 244
- 125000000217 alkyl group Chemical group 0.000 claims description 238
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 238
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 220
- -1 hydroxy, amino Chemical group 0.000 claims description 178
- 229910052757 nitrogen Inorganic materials 0.000 claims description 161
- 229910052736 halogen Inorganic materials 0.000 claims description 160
- 150000002367 halogens Chemical class 0.000 claims description 160
- 150000002431 hydrogen Chemical class 0.000 claims description 116
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 111
- 238000000034 method Methods 0.000 claims description 106
- 125000005842 heteroatom Chemical group 0.000 claims description 99
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 99
- 229910052760 oxygen Inorganic materials 0.000 claims description 94
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 92
- 239000001301 oxygen Chemical group 0.000 claims description 92
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 85
- 229910052717 sulfur Chemical group 0.000 claims description 85
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 81
- 239000011593 sulfur Chemical group 0.000 claims description 81
- 125000003118 aryl group Chemical group 0.000 claims description 75
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 65
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 63
- 229910052799 carbon Inorganic materials 0.000 claims description 63
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 59
- 229910052720 vanadium Inorganic materials 0.000 claims description 46
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 44
- 125000003282 alkyl amino group Chemical group 0.000 claims description 40
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 27
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 25
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 150000003852 triazoles Chemical class 0.000 claims description 17
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 11
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 11
- 201000004681 Psoriasis Diseases 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 319
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 215
- 239000000243 solution Substances 0.000 description 184
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- 229940093499 ethyl acetate Drugs 0.000 description 107
- 235000019439 ethyl acetate Nutrition 0.000 description 106
- 239000007787 solid Substances 0.000 description 105
- 238000006243 chemical reaction Methods 0.000 description 100
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
- 239000000203 mixture Substances 0.000 description 76
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 70
- 238000002360 preparation method Methods 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 60
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 54
- 239000007858 starting material Substances 0.000 description 53
- 229960004132 diethyl ether Drugs 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 48
- 239000012267 brine Substances 0.000 description 47
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 45
- 125000003545 alkoxy group Chemical group 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 42
- 239000010410 layer Substances 0.000 description 41
- 230000002829 reductive effect Effects 0.000 description 40
- 239000012442 inert solvent Substances 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 30
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- 239000003208 petroleum Substances 0.000 description 25
- 239000000706 filtrate Substances 0.000 description 24
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
- 238000007796 conventional method Methods 0.000 description 21
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 150000002148 esters Chemical class 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 230000008569 process Effects 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 102100025390 Integrin beta-2 Human genes 0.000 description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 239000000284 extract Substances 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 108010064548 Lymphocyte Function-Associated Antigen-1 Proteins 0.000 description 10
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 9
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical class CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 230000004927 fusion Effects 0.000 description 9
- 230000004048 modification Effects 0.000 description 9
- 238000012986 modification Methods 0.000 description 9
- 229910000510 noble metal Inorganic materials 0.000 description 9
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 9
- 229940074439 potassium sodium tartrate Drugs 0.000 description 9
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 9
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 239000012065 filter cake Substances 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- 238000006467 substitution reaction Methods 0.000 description 7
- 150000003512 tertiary amines Chemical class 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- OMNHTTWQSSUZHO-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(C)=C1O OMNHTTWQSSUZHO-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000006044 T cell activation Effects 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 239000012948 isocyanate Substances 0.000 description 6
- 150000002513 isocyanates Chemical class 0.000 description 6
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
- 125000004193 piperazinyl group Chemical group 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- 125000004463 2,4-dimethyl-thiazol-5-yl group Chemical group CC=1SC(=C(N1)C)* 0.000 description 5
- GNKXSFMQOJYWFR-UHFFFAOYSA-N 2-chloro-4-[3-(3-hydroxyphenyl)propanoyl]benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=CC=C1C(=O)CCC1=CC=CC(O)=C1 GNKXSFMQOJYWFR-UHFFFAOYSA-N 0.000 description 5
- KLEYVGWAORGTIT-UHFFFAOYSA-N 2-chlorothiazole Chemical compound ClC1=NC=CS1 KLEYVGWAORGTIT-UHFFFAOYSA-N 0.000 description 5
- IHWMWEIAAARWJH-UHFFFAOYSA-N 3-chloro-4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1Cl IHWMWEIAAARWJH-UHFFFAOYSA-N 0.000 description 5
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 5
- 108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 5
- 102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 235000005513 chalcones Nutrition 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
- 230000001590 oxidative effect Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- WNOPIURUTIVUBE-UHFFFAOYSA-N (3-hydroxyphenyl)methylazanium;chloride Chemical compound Cl.NCC1=CC=CC(O)=C1 WNOPIURUTIVUBE-UHFFFAOYSA-N 0.000 description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- PCFLQDJHCZHSGG-UHFFFAOYSA-N 1h-indol-4-ylmethanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC2=C1C=CN2 PCFLQDJHCZHSGG-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- AULKDLUOQCUNOK-UHFFFAOYSA-N 3,5-dichloro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC(Cl)=C(O)C(Cl)=C1 AULKDLUOQCUNOK-UHFFFAOYSA-N 0.000 description 4
- ZJGOZXACDNCTSA-UHFFFAOYSA-N 3-bromo-4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1Br ZJGOZXACDNCTSA-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 4
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 4
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- GMWGOKDYTQHLRL-UHFFFAOYSA-N [3-[tert-butyl(dimethyl)silyl]oxyphenyl]methanamine Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(CN)=C1 GMWGOKDYTQHLRL-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
- 229910002091 carbon monoxide Inorganic materials 0.000 description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- ALNFWXQKGZXCPT-UHFFFAOYSA-N ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(NC(=O)OC(C)(C)C)=NC=1C(F)(F)F ALNFWXQKGZXCPT-UHFFFAOYSA-N 0.000 description 4
- MRTLEHHSTAFINK-UHFFFAOYSA-N ethyl 4-methyl-2-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C(C)C)=NC=1C MRTLEHHSTAFINK-UHFFFAOYSA-N 0.000 description 4
- IYWKKZAAUKWYNT-UHFFFAOYSA-N ethyl 4-propan-2-yl-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC(C(C)C)=CS1 IYWKKZAAUKWYNT-UHFFFAOYSA-N 0.000 description 4
- QUMFJYBJMPXPBS-UHFFFAOYSA-N ethyl 4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC=NC=1C(C)C QUMFJYBJMPXPBS-UHFFFAOYSA-N 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011888 foil Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000005304 joining Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 150000004702 methyl esters Chemical class 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 229930189471 penicacid Natural products 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 4
- 229910052721 tungsten Inorganic materials 0.000 description 4
- RTCUCQWIICFPOD-SECBINFHSA-N (1r)-1-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C([C@H](N)C)=CC=CC2=C1 RTCUCQWIICFPOD-SECBINFHSA-N 0.000 description 3
- IELFLNFBTDIHQI-UHFFFAOYSA-N (2-ethyl-4-methyl-1,3-thiazol-5-yl)methanol Chemical compound CCC1=NC(C)=C(CO)S1 IELFLNFBTDIHQI-UHFFFAOYSA-N 0.000 description 3
- FDKIIQDTRBIUCI-UHFFFAOYSA-N (4-propan-2-yl-1,3-thiazol-5-yl)methanol Chemical compound CC(C)C=1N=CSC=1CO FDKIIQDTRBIUCI-UHFFFAOYSA-N 0.000 description 3
- ZXRLWHGLEJGMNO-UHFFFAOYSA-N 1,3-thiazole-5-carbaldehyde Chemical compound O=CC1=CN=CS1 ZXRLWHGLEJGMNO-UHFFFAOYSA-N 0.000 description 3
- KUZHMEJORCJMII-UHFFFAOYSA-N 1-(3-chloro-4-methoxycarbonylphenyl)-2-diazonioethenolate Chemical compound COC(=O)C1=CC=C(C([O-])=C[N+]#N)C=C1Cl KUZHMEJORCJMII-UHFFFAOYSA-N 0.000 description 3
- BVSGXWCTWBZFEV-UHFFFAOYSA-N 1h-indol-4-ylmethanol Chemical compound OCC1=CC=CC2=C1C=CN2 BVSGXWCTWBZFEV-UHFFFAOYSA-N 0.000 description 3
- FURRUNQWZZOXOT-UHFFFAOYSA-N 1h-indol-6-ylmethanamine Chemical compound NCC1=CC=C2C=CNC2=C1 FURRUNQWZZOXOT-UHFFFAOYSA-N 0.000 description 3
- ZOPJEHPVWLTDJW-UHFFFAOYSA-N 2-(dimethylamino)-1,3-thiazole-5-carbaldehyde Chemical compound CN(C)C1=NC=C(C=O)S1 ZOPJEHPVWLTDJW-UHFFFAOYSA-N 0.000 description 3
- PKCBQQXHFIDIIG-UHFFFAOYSA-N 2-chloro-1,3-thiazole-5-carbaldehyde Chemical compound ClC1=NC=C(C=O)S1 PKCBQQXHFIDIIG-UHFFFAOYSA-N 0.000 description 3
- TZHSDLDOOZAFAL-UHFFFAOYSA-N 2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propyl]benzoic acid Chemical compound C=1C=C(C(O)=O)C(Cl)=CC=1C(O)CCC1=CC=CC(O)=C1 TZHSDLDOOZAFAL-UHFFFAOYSA-N 0.000 description 3
- NPCLRBQYESMUPD-UHFFFAOYSA-N 2-methylpropanethioamide Chemical compound CC(C)C(N)=S NPCLRBQYESMUPD-UHFFFAOYSA-N 0.000 description 3
- APEHZRBOJCLRPY-UHFFFAOYSA-N 2-piperazin-1-yl-1,3-thiazole-5-carbaldehyde Chemical compound S1C(C=O)=CN=C1N1CCNCC1 APEHZRBOJCLRPY-UHFFFAOYSA-N 0.000 description 3
- ULRPISSMEBPJLN-UHFFFAOYSA-N 2h-tetrazol-5-amine Chemical compound NC1=NN=NN1 ULRPISSMEBPJLN-UHFFFAOYSA-N 0.000 description 3
- HEPDHTNDZDMUBB-UHFFFAOYSA-N 3,5-dichloro-4-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=C(Cl)C=C(C(O)=O)C=C1Cl HEPDHTNDZDMUBB-UHFFFAOYSA-N 0.000 description 3
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 description 3
- NFYVSBBZWOIZDU-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxybenzonitrile Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(C#N)=C1 NFYVSBBZWOIZDU-UHFFFAOYSA-N 0.000 description 3
- UFWGXFOKGNJAOS-UHFFFAOYSA-N 3-chloro-4-hydroxy-5-methylbenzaldehyde Chemical compound CC1=CC(C=O)=CC(Cl)=C1O UFWGXFOKGNJAOS-UHFFFAOYSA-N 0.000 description 3
- VNYDGBJJSKBZKW-UHFFFAOYSA-N 3-chloro-4-hydroxy-5-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(Cl)=C1O VNYDGBJJSKBZKW-UHFFFAOYSA-N 0.000 description 3
- UDWDIOPWZFNDKK-UHFFFAOYSA-N 4-(azidomethyl)-1h-indole Chemical compound [N-]=[N+]=NCC1=CC=CC2=C1C=CN2 UDWDIOPWZFNDKK-UHFFFAOYSA-N 0.000 description 3
- HFCRSABBNBNZNG-UHFFFAOYSA-N 4-methoxycarbonyl-3-methylbenzoic acid Chemical compound COC(=O)C1=CC=C(C(O)=O)C=C1C HFCRSABBNBNZNG-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 101000935040 Homo sapiens Integrin beta-2 Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 3
- 229910052770 Uranium Inorganic materials 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- IYNBZFZLXYMQEF-UHFFFAOYSA-N benzotriazole-1,5-dicarboxylic acid Chemical compound OC(=O)C1=CC=C2N(C(O)=O)N=NC2=C1 IYNBZFZLXYMQEF-UHFFFAOYSA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- XJRPTMORGOIMMI-UHFFFAOYSA-N ethyl 2-amino-4-(trifluoromethyl)-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(N)=NC=1C(F)(F)F XJRPTMORGOIMMI-UHFFFAOYSA-N 0.000 description 3
- AUWPEXCKPSIEIX-UHFFFAOYSA-N ethyl 2-chloro-4-methyl-3-oxopentanoate Chemical compound CCOC(=O)C(Cl)C(=O)C(C)C AUWPEXCKPSIEIX-UHFFFAOYSA-N 0.000 description 3
- GCSPDEIDKWHUFE-UHFFFAOYSA-N ethyl 2-methyl-4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1C(C)C GCSPDEIDKWHUFE-UHFFFAOYSA-N 0.000 description 3
- LNOHWUBYLHGSNL-UHFFFAOYSA-N ethyl 4-chloro-4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)(C)Cl LNOHWUBYLHGSNL-UHFFFAOYSA-N 0.000 description 3
- XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 3
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- NMILWYUYIFMKTE-UHFFFAOYSA-N methyl 1-methylindole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CN(C)C2=C1 NMILWYUYIFMKTE-UHFFFAOYSA-N 0.000 description 3
- CJJRCXIZONPLDD-VMPITWQZSA-N methyl 2-chloro-4-[(e)-3-(3-hydroxyphenyl)prop-2-enoyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)\C=C\C1=CC=CC(O)=C1 CJJRCXIZONPLDD-VMPITWQZSA-N 0.000 description 3
- QMJHHUCQAPQBAW-UHFFFAOYSA-N methyl 4-(2-bromoacetyl)-2-chlorobenzoate Chemical compound COC(=O)C1=CC=C(C(=O)CBr)C=C1Cl QMJHHUCQAPQBAW-UHFFFAOYSA-N 0.000 description 3
- USFWBPHOAJDWHM-UHFFFAOYSA-N n-[[3-[tert-butyl(dimethyl)silyl]oxyphenyl]methyl]-4-hydroxy-3,5-dimethylbenzamide Chemical compound CC1=C(O)C(C)=CC(C(=O)NCC=2C=C(O[Si](C)(C)C(C)(C)C)C=CC=2)=C1 USFWBPHOAJDWHM-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- ZEJPMRKECMRICL-UHFFFAOYSA-N o-ethyl 2-amino-2-oxoethanethioate Chemical compound CCOC(=S)C(N)=O ZEJPMRKECMRICL-UHFFFAOYSA-N 0.000 description 3
- 239000010502 orange oil Substances 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical class ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 3
- VBQCHPIMZGQLAZ-UHFFFAOYSA-N phosphorane Chemical compound [PH5] VBQCHPIMZGQLAZ-UHFFFAOYSA-N 0.000 description 3
- 229920005862 polyol Polymers 0.000 description 3
- 150000003077 polyols Chemical class 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical class ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- YDMPSBJXPPXTCM-UHFFFAOYSA-N (1-methylindol-6-yl)methanol Chemical compound C1=C(CO)C=C2N(C)C=CC2=C1 YDMPSBJXPPXTCM-UHFFFAOYSA-N 0.000 description 2
- BRQKYVQSAUQHNC-UHFFFAOYSA-N (2,4-dimethyl-1,3-thiazol-5-yl)methanol Chemical compound CC1=NC(C)=C(CO)S1 BRQKYVQSAUQHNC-UHFFFAOYSA-N 0.000 description 2
- AJBSHCALQMLUSD-UHFFFAOYSA-N (2-ethyl-4-propan-2-yl-1,3-thiazol-5-yl)methanol Chemical compound CCC1=NC(C(C)C)=C(CO)S1 AJBSHCALQMLUSD-UHFFFAOYSA-N 0.000 description 2
- KRCIFTBSQKDYMH-UHFFFAOYSA-N (2-methyl-1,3-thiazol-4-yl)methanol Chemical compound CC1=NC(CO)=CS1 KRCIFTBSQKDYMH-UHFFFAOYSA-N 0.000 description 2
- UZJGVBSSFLTCNQ-UHFFFAOYSA-N (2-thiophen-2-yl-1,3-thiazol-5-yl)methanol Chemical compound S1C(CO)=CN=C1C1=CC=CS1 UZJGVBSSFLTCNQ-UHFFFAOYSA-N 0.000 description 2
- RNVABPBNHNPLKY-UHFFFAOYSA-N (4-methyl-2-propan-2-yl-1,3-thiazol-5-yl)methanol Chemical compound CC(C)C1=NC(C)=C(CO)S1 RNVABPBNHNPLKY-UHFFFAOYSA-N 0.000 description 2
- YJTSEYDGJPGJPR-UHFFFAOYSA-N (4-propan-2-yl-1,3-thiazol-2-yl)methanol Chemical compound CC(C)C1=CSC(CO)=N1 YJTSEYDGJPGJPR-UHFFFAOYSA-N 0.000 description 2
- GTXOEWBQGFBPFD-NHDPSOOVSA-N (z)-2-[[2-bromo-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=3C=CNC=3C=CC=2)C=C1Br GTXOEWBQGFBPFD-NHDPSOOVSA-N 0.000 description 2
- ASYIZQYCKWVVBI-YVLHZVERSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(1,3-thiazol-2-yl)prop-2-enoic acid Chemical compound N=1C=CSC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 ASYIZQYCKWVVBI-YVLHZVERSA-N 0.000 description 2
- JXJBFHFBLYUUKA-LSCVHKIXSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(1h-imidazol-5-yl)prop-2-enoic acid Chemical compound C=1NC=NC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 JXJBFHFBLYUUKA-LSCVHKIXSA-N 0.000 description 2
- YLQJGGYNXONXTM-NDENLUEZSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2-hydroxyphenyl)prop-2-enoic acid Chemical compound C=1C=CC=C(O)C=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 YLQJGGYNXONXTM-NDENLUEZSA-N 0.000 description 2
- XOWHWVCUMXYEQA-MTJSOVHGSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2-morpholin-4-yl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound C=1N=C(N2CCOCC2)SC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 XOWHWVCUMXYEQA-MTJSOVHGSA-N 0.000 description 2
- SVWODFGVQHMSNZ-MTJSOVHGSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2-piperazin-1-yl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound C=1N=C(N2CCNCC2)SC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 SVWODFGVQHMSNZ-MTJSOVHGSA-N 0.000 description 2
- PCNPAHHBGGKKQZ-OCKHKDLRSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(furan-3-yl)prop-2-enoic acid Chemical compound C1=COC=C1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 PCNPAHHBGGKKQZ-OCKHKDLRSA-N 0.000 description 2
- GSXDNHRGJLNFFY-GRSHGNNSSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-[2-(dimethylamino)-1,3-thiazol-5-yl]prop-2-enoic acid Chemical compound S1C(N(C)C)=NC=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Br GSXDNHRGJLNFFY-GRSHGNNSSA-N 0.000 description 2
- QVXPWWKYKWRMMT-MTJSOVHGSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-phenylprop-2-enoic acid Chemical compound C=1C=CC=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 QVXPWWKYKWRMMT-MTJSOVHGSA-N 0.000 description 2
- YVAPRXDUAPMMAJ-NDENLUEZSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-pyridin-2-ylprop-2-enoic acid Chemical compound C=1C=CC=NC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 YVAPRXDUAPMMAJ-NDENLUEZSA-N 0.000 description 2
- COXLRWSBQFTWFZ-JMIUGGIZSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-pyridin-3-ylprop-2-enoic acid Chemical compound C=1C=CN=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 COXLRWSBQFTWFZ-JMIUGGIZSA-N 0.000 description 2
- UYNWMJUFAXEJTC-JAIQZWGSSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-pyridin-4-ylprop-2-enoic acid Chemical compound C=1C=NC=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 UYNWMJUFAXEJTC-JAIQZWGSSA-N 0.000 description 2
- WAUHITLDBIUOPT-OYKKKHCWSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-quinolin-2-ylprop-2-enoic acid Chemical compound C=1C=C2C=CC=CC2=NC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 WAUHITLDBIUOPT-OYKKKHCWSA-N 0.000 description 2
- OQFAAOVELJCJHL-ODLFYWEKSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-thiophen-2-ylprop-2-enoic acid Chemical compound C=1C=CSC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 OQFAAOVELJCJHL-ODLFYWEKSA-N 0.000 description 2
- NJOFVFQIGWZHOG-OCKHKDLRSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-thiophen-3-ylprop-2-enoic acid Chemical compound C1=CSC=C1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 NJOFVFQIGWZHOG-OCKHKDLRSA-N 0.000 description 2
- CKQVOZHCJAOSLT-INGKJJEOSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]pent-2-enoic acid Chemical compound C1=C(Br)C(C(=O)N\C(=C/CC)C(O)=O)=CC=C1C(=O)NCC1=CC=CC(O)=C1 CKQVOZHCJAOSLT-INGKJJEOSA-N 0.000 description 2
- XASUJRCAWMFHAT-QRVIBDJDSA-N (z)-2-[[2-chloro-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]-3-phenylprop-2-enoic acid Chemical compound C=1C=C(C(=O)NCC=2C=3C=CNC=3C=CC=2)C=C(Cl)C=1C(=O)N/C(C(=O)O)=C\C1=CC=CC=C1 XASUJRCAWMFHAT-QRVIBDJDSA-N 0.000 description 2
- DGARIVJPAYJFOP-MTJSOVHGSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]-6-methylbenzoyl]amino]-3-phenylprop-2-enoic acid Chemical compound CC1=CC(C(=O)NCC=2C=C(O)C=CC=2)=CC(Cl)=C1C(=O)N\C(C(O)=O)=C/C1=CC=CC=C1 DGARIVJPAYJFOP-MTJSOVHGSA-N 0.000 description 2
- BSEDNGNCYROORI-MSXFZWOLSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]-6-methylbenzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1C(Cl)=C(C(=O)N\C(=C/C=2C=C3C=CC=CC3=NC=2)C(O)=O)C(C)=CC=1C(=O)NCC1=CC=CC(O)=C1 BSEDNGNCYROORI-MSXFZWOLSA-N 0.000 description 2
- CECKMFNEKSMPTL-FMCGGJTJSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(1-methylindol-6-yl)prop-2-enoic acid Chemical compound C1=C2N(C)C=CC2=CC=C1\C=C(C(O)=O)/NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 CECKMFNEKSMPTL-FMCGGJTJSA-N 0.000 description 2
- YLMBVPTVNZQIGB-GRSHGNNSSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Cl YLMBVPTVNZQIGB-GRSHGNNSSA-N 0.000 description 2
- WEIBTWWFNXVOCS-IUXPMGMMSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2-chloro-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound C=1N=C(Cl)SC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 WEIBTWWFNXVOCS-IUXPMGMMSA-N 0.000 description 2
- JJLOCGHDICTHNZ-ODLFYWEKSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2-ethyl-4-methyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(CC)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Cl JJLOCGHDICTHNZ-ODLFYWEKSA-N 0.000 description 2
- CFEDBPRPZARLBA-GRSHGNNSSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(4-propan-2-yl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound N1=CSC(\C=C(/NC(=O)C=2C(=CC(=CC=2)C(=O)NCC=2C=C(O)C=CC=2)Cl)C(O)=O)=C1C(C)C CFEDBPRPZARLBA-GRSHGNNSSA-N 0.000 description 2
- NEFCDEHZKVKMMO-NHDPSOOVSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(4-sulfamoylphenyl)prop-2-enoic acid Chemical compound C1=CC(S(=O)(=O)N)=CC=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Cl NEFCDEHZKVKMMO-NHDPSOOVSA-N 0.000 description 2
- KBHWTNIGYHFQGU-SXGWCWSVSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-[2-(methylamino)-4-(trifluoromethyl)-1,3-thiazol-5-yl]prop-2-enoic acid Chemical compound S1C(NC)=NC(C(F)(F)F)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Cl KBHWTNIGYHFQGU-SXGWCWSVSA-N 0.000 description 2
- AGCJFFQWRJNVES-MTJSOVHGSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-phenylprop-2-enoic acid Chemical compound C=1C=CC=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 AGCJFFQWRJNVES-MTJSOVHGSA-N 0.000 description 2
- FWSOWCIHECXSCI-MSXFZWOLSA-N (z)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1N=C2C=CC=CC2=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 FWSOWCIHECXSCI-MSXFZWOLSA-N 0.000 description 2
- QEUGDWWTYGZZMJ-NDENLUEZSA-N (z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propyl]benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(O)CCC=2C=C(O)C=CC=2)C=C1Cl QEUGDWWTYGZZMJ-NDENLUEZSA-N 0.000 description 2
- GRRODEILYCIQDM-UKWGHVSLSA-N (z)-2-[[4-[(3,5-difluorophenyl)methylcarbamoyl]-2,6-dimethylbenzoyl]amino]-3-(5-methyl-1h-imidazol-4-yl)prop-2-enoic acid Chemical compound N1=CNC(\C=C(/NC(=O)C=2C(=CC(=CC=2C)C(=O)NCC=2C=C(F)C=C(F)C=2)C)C(O)=O)=C1C GRRODEILYCIQDM-UKWGHVSLSA-N 0.000 description 2
- YYFHIJLBAFMMQO-MSXFZWOLSA-N (z)-2-[[4-[(3-aminophenyl)methylcarbamoyl]-2-bromobenzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical group NC1=CC=CC(CNC(=O)C=2C=C(Br)C(C(=O)N\C(=C/C=3C=C4C=CC=CC4=NC=3)C(O)=O)=CC=2)=C1 YYFHIJLBAFMMQO-MSXFZWOLSA-N 0.000 description 2
- DNKVMXXWVSZGFH-OYKKKHCWSA-N (z)-2-[[4-[(3-hydroxyphenyl)methylcarbamoyl]-2-methylbenzoyl]amino]-3-(1h-indol-6-yl)prop-2-enoic acid Chemical compound C=1C=C(C(=O)N\C(=C/C=2C=C3NC=CC3=CC=2)C(O)=O)C(C)=CC=1C(=O)NCC1=CC=CC(O)=C1 DNKVMXXWVSZGFH-OYKKKHCWSA-N 0.000 description 2
- UZPAYZPHRHQEKR-HMAPJEAMSA-N (z)-2-[[4-[(3-hydroxyphenyl)methylcarbamoyl]-2-methylbenzoyl]amino]-3-phenylprop-2-enoic acid Chemical compound CC1=CC(C(=O)NCC=2C=C(O)C=CC=2)=CC=C1C(=O)N\C(C(O)=O)=C/C1=CC=CC=C1 UZPAYZPHRHQEKR-HMAPJEAMSA-N 0.000 description 2
- KZOJROVNXKLKRW-QFEZKATASA-N (z)-2-[[4-[(3-hydroxyphenyl)methylcarbamoyl]-2-methylbenzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1C=C(C(=O)N\C(=C/C=2C=C3C=CC=CC3=NC=2)C(O)=O)C(C)=CC=1C(=O)NCC1=CC=CC(O)=C1 KZOJROVNXKLKRW-QFEZKATASA-N 0.000 description 2
- IDCVXIQEKOHZSP-NDENLUEZSA-N (z)-3-(1,3-benzothiazol-2-yl)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound N=1C2=CC=CC=C2SC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 IDCVXIQEKOHZSP-NDENLUEZSA-N 0.000 description 2
- MPLQHDNBWZZMES-RMORIDSASA-N (z)-3-(1,3-benzothiazol-6-yl)-2-[[2-bromo-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]prop-2-enoic acid Chemical compound C1=C2N=CSC2=CC(/C=C(\NC(=O)C=2C(=CC(=CC=2)C(=O)NCC=2C=3C=CNC=3C=CC=2)Br)C(=O)O)=C1 MPLQHDNBWZZMES-RMORIDSASA-N 0.000 description 2
- UVYDUTKLEDBPOJ-NKVSQWTQSA-N (z)-3-(1,3-benzothiazol-6-yl)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C=1C=C2N=CSC2=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 UVYDUTKLEDBPOJ-NKVSQWTQSA-N 0.000 description 2
- DQCJMRMVVKPEIT-UUYOSTAYSA-N (z)-3-(1-benzothiophen-3-yl)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C=1SC2=CC=CC=C2C=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 DQCJMRMVVKPEIT-UUYOSTAYSA-N 0.000 description 2
- OUONDYUMDBCQRO-FBHDLOMBSA-N (z)-3-(2,1,3-benzoxadiazol-5-yl)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C1=CC2=NON=C2C=C1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 OUONDYUMDBCQRO-FBHDLOMBSA-N 0.000 description 2
- SZWBBUOYTUVNRP-JAIQZWGSSA-N (z)-3-(2,4-dimethyl-1,3-thiazol-5-yl)-2-[[4-[(3-hydroxyphenyl)methylcarbamoyl]-2,6-dimethylbenzoyl]amino]prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=C(C)C=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1C SZWBBUOYTUVNRP-JAIQZWGSSA-N 0.000 description 2
- ZUWIUCXIJNEAFQ-IUXPMGMMSA-N (z)-3-(2-amino-1,3-thiazol-5-yl)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound S1C(N)=NC=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Br ZUWIUCXIJNEAFQ-IUXPMGMMSA-N 0.000 description 2
- ZBVBTSRCUUKUOJ-KSEXSDGBSA-N (z)-3-(2h-benzotriazol-5-yl)-2-[[2-bromo-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]prop-2-enoic acid Chemical compound C1=C2N=NNC2=CC(/C=C(\NC(=O)C=2C(=CC(=CC=2)C(=O)NCC=2C=3C=CNC=3C=CC=2)Br)C(=O)O)=C1 ZBVBTSRCUUKUOJ-KSEXSDGBSA-N 0.000 description 2
- VXSYCMORWJFQNP-FBHDLOMBSA-N (z)-3-(2h-benzotriazol-5-yl)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C=1C=C2NN=NC2=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 VXSYCMORWJFQNP-FBHDLOMBSA-N 0.000 description 2
- CPJSQKUPYVYLOG-FBHDLOMBSA-N (z)-3-(2h-benzotriazol-5-yl)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]-6-methylbenzoyl]amino]prop-2-enoic acid Chemical compound C=1C(Cl)=C(C(=O)N\C(=C/C=2C=C3N=NNC3=CC=2)C(O)=O)C(C)=CC=1C(=O)NCC1=CC=CC(O)=C1 CPJSQKUPYVYLOG-FBHDLOMBSA-N 0.000 description 2
- OWNGYLAAZWNKQL-UUYOSTAYSA-N (z)-3-(2h-benzotriazol-5-yl)-2-[[4-[(3-hydroxyphenyl)methylcarbamoyl]-2,6-dimethylbenzoyl]amino]prop-2-enoic acid Chemical compound C=1C(C)=C(C(=O)N\C(=C/C=2C=C3N=NNC3=CC=2)C(O)=O)C(C)=CC=1C(=O)NCC1=CC=CC(O)=C1 OWNGYLAAZWNKQL-UUYOSTAYSA-N 0.000 description 2
- BWABWWNCFTWQBC-ZBKNUEDVSA-N (z)-3-(6-chloro-1,3-benzodioxol-5-yl)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C=1C=2OCOC=2C=C(Cl)C=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 BWABWWNCFTWQBC-ZBKNUEDVSA-N 0.000 description 2
- UUKUCWJZXDXLPG-NVNXTCNLSA-N (z)-3-[2-amino-4-(trifluoromethyl)-1,3-thiazol-5-yl]-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound S1C(N)=NC(C(F)(F)F)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Cl UUKUCWJZXDXLPG-NVNXTCNLSA-N 0.000 description 2
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
- SCCCIUGOOQLDGW-UHFFFAOYSA-N 1,1-dicyclohexylurea Chemical compound C1CCCCC1N(C(=O)N)C1CCCCC1 SCCCIUGOOQLDGW-UHFFFAOYSA-N 0.000 description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 2
- GVVHBNABFJZWIC-UHFFFAOYSA-N 1-(dichloromethoxy)butane Chemical compound CCCCOC(Cl)Cl GVVHBNABFJZWIC-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- WDJLPQCBTBZTRH-UHFFFAOYSA-N 1-benzothiophene-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CSC2=C1 WDJLPQCBTBZTRH-UHFFFAOYSA-N 0.000 description 2
- NNTPEAXKKUPBHQ-UHFFFAOYSA-N 1-bromo-3-methylbutan-2-one Chemical compound CC(C)C(=O)CBr NNTPEAXKKUPBHQ-UHFFFAOYSA-N 0.000 description 2
- IYYAAIGPQOLNLY-UHFFFAOYSA-N 1-o-tert-butyl 6-o-methyl indole-1,6-dicarboxylate Chemical compound COC(=O)C1=CC=C2C=CN(C(=O)OC(C)(C)C)C2=C1 IYYAAIGPQOLNLY-UHFFFAOYSA-N 0.000 description 2
- GHTDODSYDCPOCW-UHFFFAOYSA-N 1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=CNC2=C1 GHTDODSYDCPOCW-UHFFFAOYSA-N 0.000 description 2
- XJUBKVSCNJIWMB-UHFFFAOYSA-N 2,1,3-benzothiadiazol-5-ylmethanol Chemical compound C1=C(CO)C=CC2=NSN=C21 XJUBKVSCNJIWMB-UHFFFAOYSA-N 0.000 description 2
- MJBMABRJMSARQW-UHFFFAOYSA-N 2,6-dichloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=C(Cl)C=C1C(=O)NCC1=CC=CC(O)=C1 MJBMABRJMSARQW-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- CKILCKJKCRCDQD-UHFFFAOYSA-N 2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoic acid Chemical compound C1=C(Br)C(C(=O)O)=CC=C1C(=O)NCC1=CC=CC(O)=C1 CKILCKJKCRCDQD-UHFFFAOYSA-N 0.000 description 2
- NHEVNDJWJORHNV-UHFFFAOYSA-N 2-ethyl-4-methyl-1,3-thiazole-5-carbaldehyde Chemical compound CCC1=NC(C)=C(C=O)S1 NHEVNDJWJORHNV-UHFFFAOYSA-N 0.000 description 2
- JNZYADHPGVZMQK-UHFFFAOYSA-N 3-(aminomethyl)phenol Chemical compound NCC1=CC=CC(O)=C1 JNZYADHPGVZMQK-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
- SGHBRHKBCLLVCI-UHFFFAOYSA-N 3-hydroxybenzonitrile Chemical compound OC1=CC=CC(C#N)=C1 SGHBRHKBCLLVCI-UHFFFAOYSA-N 0.000 description 2
- MPPNCIQDXQREAQ-UHFFFAOYSA-N 4-o-(2,5-dioxopyrrolidin-1-yl) 1-o-methyl 2-chlorobenzene-1,4-dicarboxylate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)ON1C(=O)CCC1=O MPPNCIQDXQREAQ-UHFFFAOYSA-N 0.000 description 2
- CUMFTMHDINTVBT-UHFFFAOYSA-N 4-propan-2-yl-1,3-thiazole-5-carbaldehyde Chemical compound CC(C)C=1N=CSC=1C=O CUMFTMHDINTVBT-UHFFFAOYSA-N 0.000 description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
- OQJKIWLFCLQWTO-UHFFFAOYSA-N 5-(hydroxymethyl)benzotriazole-1-carboxylic acid Chemical compound OCC1=CC=C2N(C(O)=O)N=NC2=C1 OQJKIWLFCLQWTO-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 108091008874 T cell receptors Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 241000534944 Thia Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- RVWLYJBKWMOUFP-UHFFFAOYSA-M [2-(2-chloro-4-methoxycarbonylphenyl)-2-oxoethyl]-triphenylphosphanium;bromide Chemical compound [Br-].ClC1=CC(C(=O)OC)=CC=C1C(=O)C[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 RVWLYJBKWMOUFP-UHFFFAOYSA-M 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 239000012964 benzotriazole Substances 0.000 description 2
- JOAHRXPHWBIBJA-UHFFFAOYSA-N benzotriazole-1,6-dicarboxylic acid Chemical compound OC(=O)C1=CC=C2N=NN(C(O)=O)C2=C1 JOAHRXPHWBIBJA-UHFFFAOYSA-N 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000021523 carboxylation Effects 0.000 description 2
- 238000006473 carboxylation reaction Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- FUFFCPIFRICMFH-UHFFFAOYSA-N dimethyl 2-chlorobenzene-1,4-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C(Cl)=C1 FUFFCPIFRICMFH-UHFFFAOYSA-N 0.000 description 2
- OSVXSBDYLRYLIG-UHFFFAOYSA-N dioxidochlorine(.) Chemical compound O=Cl=O OSVXSBDYLRYLIG-UHFFFAOYSA-N 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- RDULEYWUGKOCMR-UHFFFAOYSA-N ethyl 2-chloro-3-oxobutanoate Chemical compound CCOC(=O)C(Cl)C(C)=O RDULEYWUGKOCMR-UHFFFAOYSA-N 0.000 description 2
- JPMQBORRLKYYPC-UHFFFAOYSA-N ethyl 2-ethyl-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(CC)=NC=1C JPMQBORRLKYYPC-UHFFFAOYSA-N 0.000 description 2
- PSTFYCCCZHOTHW-UHFFFAOYSA-N ethyl 4-(trifluoromethyl)-1,3-thiazole-2-carboxylate Chemical compound CCOC(=O)C1=NC(C(F)(F)F)=CS1 PSTFYCCCZHOTHW-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004312 hexamethylene tetramine Substances 0.000 description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- WFKAJVHLWXSISD-UHFFFAOYSA-N isobutyramide Chemical compound CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019988 mead Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- WEAXQUBYRSEBJD-UHFFFAOYSA-N methyl 1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2 WEAXQUBYRSEBJD-UHFFFAOYSA-N 0.000 description 2
- XEBOTYUBWVQDQB-UHFFFAOYSA-N methyl 2,6-dichloro-4-[(3-methoxyphenyl)methylcarbamoyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=C(Cl)C=C1C(=O)NCC1=CC=CC(OC)=C1 XEBOTYUBWVQDQB-UHFFFAOYSA-N 0.000 description 2
- RELSQEWTTFNKBE-UHFFFAOYSA-N methyl 2-bromo-4-(1h-indol-4-ylmethylcarbamoyl)benzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC2=C1C=CN2 RELSQEWTTFNKBE-UHFFFAOYSA-N 0.000 description 2
- YMNSGIZSBVCXIK-UHFFFAOYSA-N methyl 2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC(O)=C1 YMNSGIZSBVCXIK-UHFFFAOYSA-N 0.000 description 2
- OAFJEDQUSSIBLP-UHFFFAOYSA-N methyl 2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC(O)=C1 OAFJEDQUSSIBLP-UHFFFAOYSA-N 0.000 description 2
- LDSSNOAZVVQVGJ-UHFFFAOYSA-N methyl 2-chloro-4-[3-(3-hydroxyphenyl)propanoyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)CCC1=CC=CC(O)=C1 LDSSNOAZVVQVGJ-UHFFFAOYSA-N 0.000 description 2
- ZHMNIZDZUQYTKG-CYBMUJFWSA-N methyl 2-chloro-4-[[(1r)-1-naphthalen-1-ylethyl]carbamoyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)N[C@H](C)C1=CC=CC2=CC=CC=C12 ZHMNIZDZUQYTKG-CYBMUJFWSA-N 0.000 description 2
- DRVWLCJENONGIC-UHFFFAOYSA-N methyl 4-[(3-aminophenyl)methylcarbamoyl]-2-bromobenzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC(N)=C1 DRVWLCJENONGIC-UHFFFAOYSA-N 0.000 description 2
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002828 nitro derivatives Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical compound CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 2
- 229960002218 sodium chlorite Drugs 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 2
- YEAUXZCJVQJYFI-UHFFFAOYSA-N tert-butyl n-[5-(hydroxymethyl)-4-(trifluoromethyl)-1,3-thiazol-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC(C(F)(F)F)=C(CO)S1 YEAUXZCJVQJYFI-UHFFFAOYSA-N 0.000 description 2
- ZASYEJHQQQMRPS-UHFFFAOYSA-N tert-butyl n-[5-formyl-4-(trifluoromethyl)-1,3-thiazol-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC(C(F)(F)F)=C(C=O)S1 ZASYEJHQQQMRPS-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 2
- 150000003556 thioamides Chemical class 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical class OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 2
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- VJNGGOMRUHYAMC-UHFFFAOYSA-N (3,5-difluorophenyl)methanamine Chemical compound NCC1=CC(F)=CC(F)=C1 VJNGGOMRUHYAMC-UHFFFAOYSA-N 0.000 description 1
- JISPGFYJPXGNBY-UHFFFAOYSA-N (3,5-dimethyl-1,2-oxazol-4-yl)methanol Chemical compound CC1=NOC(C)=C1CO JISPGFYJPXGNBY-UHFFFAOYSA-N 0.000 description 1
- GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 description 1
- CIUYJYRQKYGNQP-UHFFFAOYSA-N (3-nitrophenyl)methanamine Chemical compound NCC1=CC=CC([N+]([O-])=O)=C1 CIUYJYRQKYGNQP-UHFFFAOYSA-N 0.000 description 1
- PJDGHEQYXIZMOI-ZMFRSBBQSA-N (z)-2-[[2-bromo-4-(1h-indol-6-ylmethylcarbamoyl)benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C1=CC=CC2=CC(/C=C(\NC(=O)C=3C(=CC(=CC=3)C(=O)NCC=3C=C4NC=CC4=CC=3)Br)C(=O)O)=CN=C21 PJDGHEQYXIZMOI-ZMFRSBBQSA-N 0.000 description 1
- GUEOVEQUJUNHGZ-GRSHGNNSSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)NCC=2C=C(O)C=CC=2)C=C1Br GUEOVEQUJUNHGZ-GRSHGNNSSA-N 0.000 description 1
- ZJXFGCOPQCMIPQ-MFOYZWKCSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-(4-methylthiadiazol-5-yl)prop-2-enoic acid Chemical compound N1=NSC(\C=C(/NC(=O)C=2C(=CC(=CC=2)C(=O)NCC=2C=C(O)C=CC=2)Br)C(O)=O)=C1C ZJXFGCOPQCMIPQ-MFOYZWKCSA-N 0.000 description 1
- KMJGZBQVINFBIU-QFEZKATASA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-naphthalen-2-ylprop-2-enoic acid Chemical compound C=1C=C2C=CC=CC2=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 KMJGZBQVINFBIU-QFEZKATASA-N 0.000 description 1
- FNHSTWVZPMFPIN-JAIQZWGSSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-piperidin-4-ylprop-2-enoic acid Chemical compound C1CNCCC1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 FNHSTWVZPMFPIN-JAIQZWGSSA-N 0.000 description 1
- YSWDAUSTSBERKL-MSXFZWOLSA-N (z)-2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1N=C2C=CC=CC2=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Br)=CC=C1C(=O)NCC1=CC=CC(O)=C1 YSWDAUSTSBERKL-MSXFZWOLSA-N 0.000 description 1
- CKHDIZJNZCMHDT-XKZIYDEJSA-N (z)-2-[[2-chloro-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]-3-(2-hydroxyphenyl)prop-2-enoic acid Chemical compound C=1C=C(C(=O)NCC=2C=3C=CNC=3C=CC=2)C=C(Cl)C=1C(=O)N/C(C(=O)O)=C\C1=CC=CC=C1O CKHDIZJNZCMHDT-XKZIYDEJSA-N 0.000 description 1
- FUZJEGQECXTIJV-DICXZTSXSA-N (z)-2-[[2-chloro-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]-3-naphthalen-2-ylprop-2-enoic acid Chemical compound C1=CC=CC2=CC(/C=C(\NC(=O)C=3C(=CC(=CC=3)C(=O)NCC=3C=4C=CNC=4C=CC=3)Cl)C(=O)O)=CC=C21 FUZJEGQECXTIJV-DICXZTSXSA-N 0.000 description 1
- PAJQBZQJTAMDCC-MTJSOVHGSA-N (z)-2-[[2-chloro-4-(1h-indol-4-ylmethylcarbamoyl)benzoyl]amino]-3-thiophen-2-ylprop-2-enoic acid Chemical compound C=1C=C(C(=O)NCC=2C=3C=CNC=3C=CC=2)C=C(Cl)C=1C(=O)N/C(C(=O)O)=C\C1=CC=CS1 PAJQBZQJTAMDCC-MTJSOVHGSA-N 0.000 description 1
- CVJPEEJYKIOTNP-ZMFRSBBQSA-N (z)-2-[[2-chloro-4-(1h-indol-6-ylmethylcarbamoyl)benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C1=CC=CC2=CC(/C=C(\NC(=O)C=3C(=CC(=CC=3)C(=O)NCC=3C=C4NC=CC4=CC=3)Cl)C(=O)O)=CN=C21 CVJPEEJYKIOTNP-ZMFRSBBQSA-N 0.000 description 1
- LMYVJPNUJFIAIR-LRFQPHQISA-N (z)-2-[[2-chloro-4-[(e)-1-hydroxy-3-(3-hydroxyphenyl)prop-2-enyl]benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(O)\C=C\C=2C=C(O)C=CC=2)C=C1Cl LMYVJPNUJFIAIR-LRFQPHQISA-N 0.000 description 1
- LMVPBCGSJKAPGI-MPYFKCLBSA-N (z)-2-[[2-chloro-4-[(e)-1-hydroxy-3-(3-hydroxyphenyl)prop-2-enyl]benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1C=C(C(=O)N\C(=C/C=2C=C3C=CC=CC3=NC=2)C(O)=O)C(Cl)=CC=1C(O)\C=C\C1=CC=CC(O)=C1 LMVPBCGSJKAPGI-MPYFKCLBSA-N 0.000 description 1
- SCDABPSIOCUVBR-QFEZKATASA-N (z)-2-[[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propyl]benzoyl]amino]-3-quinolin-3-ylprop-2-enoic acid Chemical compound C=1C=C(C(=O)N\C(=C/C=2C=C3C=CC=CC3=NC=2)C(O)=O)C(Cl)=CC=1C(O)CCC1=CC=CC(O)=C1 SCDABPSIOCUVBR-QFEZKATASA-N 0.000 description 1
- BWWGZULOJSRBIO-NDENLUEZSA-N (z)-2-[[2-chloro-4-[3-(3-hydroxyphenyl)propanoyl]benzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=CC=C(C(=O)CCC=2C=C(O)C=CC=2)C=C1Cl BWWGZULOJSRBIO-NDENLUEZSA-N 0.000 description 1
- QWAQAGJMLYDAOH-JMIUGGIZSA-N (z)-2-[[4-[(3,5-difluorophenyl)methylcarbamoyl]-2,6-dimethylbenzoyl]amino]-3-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound S1C(C)=NC(C)=C1\C=C(C(O)=O)/NC(=O)C1=C(C)C=C(C(=O)NCC=2C=C(F)C=C(F)C=2)C=C1C QWAQAGJMLYDAOH-JMIUGGIZSA-N 0.000 description 1
- BPOMJZAKTRTFRI-NHDPSOOVSA-N (z)-3-(4-bromophenyl)-2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C=1C=C(Br)C=CC=1/C=C(C(=O)O)\NC(=O)C(C(=C1)Cl)=CC=C1C(=O)NCC1=CC=CC(O)=C1 BPOMJZAKTRTFRI-NHDPSOOVSA-N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- DMPZJACLHDWUFS-UHFFFAOYSA-N 1,3-benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2N=CSC2=C1 DMPZJACLHDWUFS-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CBZMFUPMGKSEHU-UHFFFAOYSA-N 1-bromo-4-fluoro-3,3-bis(fluoromethyl)butan-2-one Chemical compound FCC(CF)(CF)C(=O)CBr CBZMFUPMGKSEHU-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- ROGHUJUFCRFUSO-UHFFFAOYSA-N 1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CN2 ROGHUJUFCRFUSO-UHFFFAOYSA-N 0.000 description 1
- SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-UHFFFAOYSA-N 0.000 description 1
- WZUFYJFTOVGJJT-UHFFFAOYSA-N 2,1,3-benzoxadiazole-5-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC2=NON=C21 WZUFYJFTOVGJJT-UHFFFAOYSA-N 0.000 description 1
- GXCHOJJKQVPMAI-UHFFFAOYSA-N 2-(2,4-dimethyl-1,3-thiazol-5-yl)prop-2-enoic acid Chemical compound CC=1SC(=C(N1)C)C(C(=O)O)=C GXCHOJJKQVPMAI-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- HPSMZJCCJTWZRA-UHFFFAOYSA-N 2-[[2-bromo-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C1=C(Br)C(C(=O)NC(=C)C(=O)O)=CC=C1C(=O)NCC1=CC=CC(O)=C1 HPSMZJCCJTWZRA-UHFFFAOYSA-N 0.000 description 1
- LGARVNLUUZKGBF-UHFFFAOYSA-N 2-[[2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoyl]amino]prop-2-enoic acid Chemical compound C1=C(Cl)C(C(=O)NC(=C)C(=O)O)=CC=C1C(=O)NCC1=CC=CC(O)=C1 LGARVNLUUZKGBF-UHFFFAOYSA-N 0.000 description 1
- VXJOILBSROPACZ-UHFFFAOYSA-N 2-chloro-4-[(3-hydroxyphenyl)methylcarbamoyl]benzoic acid Chemical compound C1=C(Cl)C(C(=O)O)=CC=C1C(=O)NCC1=CC=CC(O)=C1 VXJOILBSROPACZ-UHFFFAOYSA-N 0.000 description 1
- QWCGLSGLJBWZGA-UHFFFAOYSA-N 2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-enyl]benzoic acid Chemical compound C=1C=C(C(O)=O)C(Cl)=CC=1C(O)C=CC1=CC=CC(O)=C1 QWCGLSGLJBWZGA-UHFFFAOYSA-N 0.000 description 1
- YPNZJHFXFVLXSE-UHFFFAOYSA-N 2-chloro-6-methylphenol Chemical compound CC1=CC=CC(Cl)=C1O YPNZJHFXFVLXSE-UHFFFAOYSA-N 0.000 description 1
- LRLQQERNMXHASR-UHFFFAOYSA-N 2-diphenylphosphanylpropan-2-yl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)C(C)(C)P(C=1C=CC=CC=1)C1=CC=CC=C1 LRLQQERNMXHASR-UHFFFAOYSA-N 0.000 description 1
- PTHDBHDZSMGHKF-UHFFFAOYSA-N 2-piperidin-2-ylethanol Chemical compound OCCC1CCCCN1 PTHDBHDZSMGHKF-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical group CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- TVAYXKLCEILMEA-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carbaldehyde Chemical compound CC1=NOC(C)=C1C=O TVAYXKLCEILMEA-UHFFFAOYSA-N 0.000 description 1
- ATWZNUYMQQXKFL-UHFFFAOYSA-N 3-(4-benzylphenyl)-3-oxopropanenitrile Chemical compound C1=CC(C(CC#N)=O)=CC=C1CC1=CC=CC=C1 ATWZNUYMQQXKFL-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
- UNTNRNUQVKDIPV-UHFFFAOYSA-N 3h-dithiazole Chemical compound N1SSC=C1 UNTNRNUQVKDIPV-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- MSRIZBHRUSVALK-UHFFFAOYSA-N 4-(hydroxymethyl)piperidine-1-carboxylic acid Chemical compound OCC1CCN(C(O)=O)CC1 MSRIZBHRUSVALK-UHFFFAOYSA-N 0.000 description 1
- APMTYCCNMBZFIQ-UHFFFAOYSA-N 4-[(3-aminophenyl)methylcarbamoyl]-2-bromobenzoic acid Chemical compound NC1=CC=CC(CNC(=O)C=2C=C(Br)C(C(O)=O)=CC=2)=C1 APMTYCCNMBZFIQ-UHFFFAOYSA-N 0.000 description 1
- PKOQDHGHQQTIDG-UHFFFAOYSA-N 4-[(3-hydroxyphenyl)methylcarbamoyl]-2-methylbenzoic acid Chemical compound C1=C(C(O)=O)C(C)=CC(C(=O)NCC=2C=C(O)C=CC=2)=C1 PKOQDHGHQQTIDG-UHFFFAOYSA-N 0.000 description 1
- MQHHXEFTOQSSDO-UHFFFAOYSA-N 4-formylpiperidine-1-carboxylic acid Chemical compound OC(=O)N1CCC(C=O)CC1 MQHHXEFTOQSSDO-UHFFFAOYSA-N 0.000 description 1
- RVPJNAGJMILZKA-UHFFFAOYSA-N 4-o-(2,5-dioxopyrrolidin-1-yl) 1-o-methyl 2-bromobenzene-1,4-dicarboxylate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)ON1C(=O)CCC1=O RVPJNAGJMILZKA-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- GGCBKPFAIUFVIV-UHFFFAOYSA-N 6-(hydroxymethyl)benzotriazole-1-carboxylic acid Chemical compound OCC1=CC=C2N=NN(C(O)=O)C2=C1 GGCBKPFAIUFVIV-UHFFFAOYSA-N 0.000 description 1
- PKVFFPSWRYBSSF-UHFFFAOYSA-N 6-formylindole-1-carboxylic acid Chemical compound C1=C(C=O)C=C2N(C(=O)O)C=CC2=C1 PKVFFPSWRYBSSF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101710145634 Antigen 1 Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 101100289995 Caenorhabditis elegans mac-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004155 Chlorine dioxide Substances 0.000 description 1
- 206010014025 Ear swelling Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- 102100022338 Integrin alpha-M Human genes 0.000 description 1
- 108010064600 Intercellular Adhesion Molecule-3 Proteins 0.000 description 1
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 description 1
- 101710148794 Intercellular adhesion molecule 2 Proteins 0.000 description 1
- 102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- FNJSWIPFHMKRAT-UHFFFAOYSA-N Monomethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(O)=O FNJSWIPFHMKRAT-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000003875 Wang resin Substances 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 1
- UBNXIXBZBNPVOD-UHFFFAOYSA-N [4-[[3-[tert-butyl(dimethyl)silyl]oxyphenyl]methylcarbamoyl]-2,6-dimethylphenyl] trifluoromethanesulfonate Chemical compound CC1=C(OS(=O)(=O)C(F)(F)F)C(C)=CC(C(=O)NCC=2C=C(O[Si](C)(C)C(C)(C)C)C=CC=2)=C1 UBNXIXBZBNPVOD-UHFFFAOYSA-N 0.000 description 1
- OFPXFNFUWXZVAB-UHFFFAOYSA-N [5-(hydroxymethyl)-4-(trifluoromethyl)-1,3-thiazol-2-yl]carbamic acid Chemical compound OCC=1SC(NC(O)=O)=NC=1C(F)(F)F OFPXFNFUWXZVAB-UHFFFAOYSA-N 0.000 description 1
- WIAPYSZAQLOLGX-UHFFFAOYSA-N [5-ethoxycarbonyl-4-(trifluoromethyl)-1,3-thiazol-2-yl]carbamic acid Chemical compound CCOC(=O)C=1SC(NC(O)=O)=NC=1C(F)(F)F WIAPYSZAQLOLGX-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 125000006242 amine protecting group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 150000001565 benzotriazoles Chemical class 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001789 chalcones Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 235000019398 chlorine dioxide Nutrition 0.000 description 1
- ZKOMQFDQFTVPBZ-UHFFFAOYSA-N cinnoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CN=NC2=C1 ZKOMQFDQFTVPBZ-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 108010047295 complement receptors Proteins 0.000 description 1
- 102000006834 complement receptors Human genes 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- XXTZHYXQVWRADW-UHFFFAOYSA-N diazomethanone Chemical compound [N]N=C=O XXTZHYXQVWRADW-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- DSSKDXUDARIMTR-UHFFFAOYSA-N dimethyl 2-aminobenzene-1,4-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C(N)=C1 DSSKDXUDARIMTR-UHFFFAOYSA-N 0.000 description 1
- VUMPFOPENBVFOF-UHFFFAOYSA-N dimethyl 2-bromobenzene-1,4-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)C(Br)=C1 VUMPFOPENBVFOF-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- BXOIIRQIGYJTTB-UHFFFAOYSA-N ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1C BXOIIRQIGYJTTB-UHFFFAOYSA-N 0.000 description 1
- RZMZBHSKPLVQCP-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate Chemical compound CCOC(=O)C(N)=O RZMZBHSKPLVQCP-UHFFFAOYSA-N 0.000 description 1
- YMBMCMOZIGSBOA-UHFFFAOYSA-N ethyl 2-amino-2-sulfanylideneacetate Chemical compound CCOC(=O)C(N)=S YMBMCMOZIGSBOA-UHFFFAOYSA-N 0.000 description 1
- PHSGBZQHGFAEHJ-UHFFFAOYSA-N ethyl 2-ethyl-4-propan-2-yl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(CC)=NC=1C(C)C PHSGBZQHGFAEHJ-UHFFFAOYSA-N 0.000 description 1
- QWWPUBQHZFHZSF-UHFFFAOYSA-N ethyl 2-methyl-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(C)=N1 QWWPUBQHZFHZSF-UHFFFAOYSA-N 0.000 description 1
- BBGQPNPEMPNTGA-UHFFFAOYSA-N ethyl 2-thiophen-2-yl-1,3-thiazole-5-carboxylate Chemical compound S1C(C(=O)OCC)=CN=C1C1=CC=CS1 BBGQPNPEMPNTGA-UHFFFAOYSA-N 0.000 description 1
- WISQBJLUORKXNY-UHFFFAOYSA-N ethyl 4-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC=NC=1C WISQBJLUORKXNY-UHFFFAOYSA-N 0.000 description 1
- AHPXTXGCMLOXGA-UHFFFAOYSA-N ethyl 4-methylthiadiazole-5-carboxylate Chemical compound CCOC(=O)C=1SN=NC=1C AHPXTXGCMLOXGA-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 150000002473 indoazoles Chemical class 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 1
- LRMFSMKHXKDUDG-UHFFFAOYSA-N methyl 2,1,3-benzothiadiazole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=NSN=C21 LRMFSMKHXKDUDG-UHFFFAOYSA-N 0.000 description 1
- XQHSISIYRCHUIA-UHFFFAOYSA-N methyl 2-bromo-4-[(3-nitrophenyl)methylcarbamoyl]benzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC([N+]([O-])=O)=C1 XQHSISIYRCHUIA-UHFFFAOYSA-N 0.000 description 1
- GWNNYXADOJAFFX-UHFFFAOYSA-N methyl 2-bromo-4-[[3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]methylcarbamoyl]benzoate Chemical compound C1=C(Br)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=CC(NC(=O)OC(C)(C)C)=C1 GWNNYXADOJAFFX-UHFFFAOYSA-N 0.000 description 1
- UETFKEIARZHTLE-UHFFFAOYSA-N methyl 2-chloro-4-(1h-indol-6-ylmethylcarbamoyl)benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(=O)NCC1=CC=C(C=CN2)C2=C1 UETFKEIARZHTLE-UHFFFAOYSA-N 0.000 description 1
- XTBFOGSLUFZCGL-VMPITWQZSA-N methyl 2-chloro-4-[(e)-1-hydroxy-3-(3-hydroxyphenyl)prop-2-enyl]benzoate Chemical compound C1=C(Cl)C(C(=O)OC)=CC=C1C(O)\C=C\C1=CC=CC(O)=C1 XTBFOGSLUFZCGL-VMPITWQZSA-N 0.000 description 1
- WVWZECQNFWFVFW-UHFFFAOYSA-N methyl 2-methylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C WVWZECQNFWFVFW-UHFFFAOYSA-N 0.000 description 1
- ZMMBQCILDZFYKX-UHFFFAOYSA-N methyl 2h-benzotriazole-5-carboxylate Chemical compound C1=C(C(=O)OC)C=CC2=NNN=C21 ZMMBQCILDZFYKX-UHFFFAOYSA-N 0.000 description 1
- CYEXEOXALMJXDI-UHFFFAOYSA-N methyl 4-bromo-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1C CYEXEOXALMJXDI-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003464 sulfur compounds Chemical group 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- JYUQEWCJWDGCRX-UHFFFAOYSA-N tert-butyl 4-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)CC1 JYUQEWCJWDGCRX-UHFFFAOYSA-N 0.000 description 1
- DWFFNTQPJJEVQG-UHFFFAOYSA-N tert-butyl 6-(hydroxymethyl)indole-1-carboxylate Chemical compound C1=C(CO)C=C2N(C(=O)OC(C)(C)C)C=CC2=C1 DWFFNTQPJJEVQG-UHFFFAOYSA-N 0.000 description 1
- ZJOBUJIAVBTRMD-UHFFFAOYSA-N tert-butyl 6-formylindole-1-carboxylate Chemical compound C1=C(C=O)C=C2N(C(=O)OC(C)(C)C)C=CC2=C1 ZJOBUJIAVBTRMD-UHFFFAOYSA-N 0.000 description 1
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 125000004950 trifluoroalkyl group Chemical group 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/85—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic unsaturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/87—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/26—Radicals substituted by carbon atoms having three bonds to hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/28—Cinnolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/16—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6524—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Quinoline Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Furan Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18118200P | 2000-02-09 | 2000-02-09 | |
US60/181,182 | 2000-02-09 |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20020073206A KR20020073206A (ko) | 2002-09-19 |
KR100710958B1 true KR100710958B1 (ko) | 2007-04-24 |
Family
ID=22663233
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020027010215A KR100710958B1 (ko) | 2000-02-09 | 2001-02-01 | 데하이드로 아미노산 |
Country Status (11)
Country | Link |
---|---|
US (1) | US6515124B2 (fr) |
EP (1) | EP1261579A1 (fr) |
JP (1) | JP2003522751A (fr) |
KR (1) | KR100710958B1 (fr) |
CN (1) | CN1257886C (fr) |
AU (2) | AU2001230227B2 (fr) |
BR (1) | BR0108240A (fr) |
CA (1) | CA2397993A1 (fr) |
MX (1) | MXPA02007461A (fr) |
WO (1) | WO2001058853A1 (fr) |
ZA (1) | ZA200205706B (fr) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6331640B1 (en) * | 1998-10-13 | 2001-12-18 | Hoffmann-La Roche Inc. | Diaminopropionic acid derivatives |
GB0028367D0 (en) * | 2000-11-21 | 2001-01-03 | Celltech Chiroscience Ltd | Chemical compounds |
WO2004002977A1 (fr) * | 2002-07-01 | 2004-01-08 | Pharmacia & Upjohn Company Llc | Inhibiteurs de la polymerase ns5b du vhc |
WO2004032861A2 (fr) | 2002-10-11 | 2004-04-22 | Bristol-Myers Squibb Company | Composes hexahydro-benzimidazolones utiles en tant qu'agents anti-inflammatoires |
EP1682537B1 (fr) | 2003-11-05 | 2012-03-28 | SARcode Bioscience Inc. | Modulateurs de l'adhesion cellulaire |
WO2005111003A1 (fr) * | 2004-04-29 | 2005-11-24 | Abbott Laboratories | Analogues d’amino-tétrazoles et méthodes d’utilisation |
CN101083982A (zh) * | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 用于治疗硬脂酰CoA去饱和酶介导的疾病的杂环衍生物 |
TW200616634A (en) | 2004-10-01 | 2006-06-01 | Bristol Myers Squibb Co | Crystalline forms and process for preparing spiro-hydantoin compounds |
US7186727B2 (en) | 2004-12-14 | 2007-03-06 | Bristol-Myers Squibb Company | Pyridyl-substituted spiro-hydantoin compounds and use thereof |
DK2444079T3 (en) * | 2005-05-17 | 2017-01-30 | Sarcode Bioscience Inc | Compositions and Methods for the Treatment of Eye Diseases |
US20090155176A1 (en) | 2007-10-19 | 2009-06-18 | Sarcode Corporation | Compositions and methods for treatment of diabetic retinopathy |
EP2276508A4 (fr) * | 2008-04-15 | 2011-12-28 | Sarcode Bioscience Inc | Administration d'antagonistes de lfa-1 au système gastro-intestinal |
US8080562B2 (en) | 2008-04-15 | 2011-12-20 | Sarcode Bioscience Inc. | Crystalline pharmaceutical and methods of preparation and use thereof |
US20090258070A1 (en) * | 2008-04-15 | 2009-10-15 | John Burnier | Topical LFA-1 antagonists for use in localized treatment of immune related disorders |
WO2009128933A1 (fr) * | 2008-04-15 | 2009-10-22 | Sarcode Corporation | Antagonistes de lfa-1 sous forme d'aérosol utilisés en traitement localisé de troubles de nature immunitaire |
US8378105B2 (en) * | 2009-10-21 | 2013-02-19 | Sarcode Bioscience Inc. | Crystalline pharmaceutical and methods of preparation and use thereof |
US20120270875A1 (en) * | 2011-03-16 | 2012-10-25 | Paul Gillespie | Pyrimidine amide compounds |
US9650363B2 (en) | 2012-01-27 | 2017-05-16 | Hoffmann-La Roche Inc. | Integrin antagonist conjugates for targeted delivery to cells expressing LFA-1 |
KR102157608B1 (ko) | 2012-07-25 | 2020-09-18 | 에스에이알코드 바이오사이언스 인코포레이티드 | Lfa-1 저해제 및 그의 다형체 |
CN106631867B (zh) * | 2016-12-27 | 2018-06-22 | 河南省科学院化学研究所有限公司 | 一种合成2-苯甲酰氨基-3-芳基丙烯酸酯的方法 |
CN112824527B (zh) * | 2019-11-20 | 2023-05-26 | 珠海联邦制药股份有限公司 | 人工设计的赖氨酰内切酶及编码序列和发酵方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0410742A1 (fr) * | 1989-07-26 | 1991-01-30 | Allergan, Inc. | Composés phényléthényliques ayant une activité semblable aux rétinoides |
US5457124A (en) | 1993-12-07 | 1995-10-10 | Hoffmann-La Roche Inc. | Carboxylic acid Leukotriene B4 antagonists |
US5559109A (en) | 1989-04-28 | 1996-09-24 | Sankko Company, Limited | Method of treating a PAF-mediated pathology or for treating or preventing psoriasis, nephritis, asthma or shock by administering a PAF antagonist |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3984428A (en) | 1968-11-22 | 1976-10-05 | Hoffmann-La Roche Inc. | Isoxazolyl-substituted perhydrobenzindenes |
JPH10175970A (ja) * | 1996-12-19 | 1998-06-30 | Mitsui Chem Inc | ベンゾチオフェン誘導体およびそれを有効成分として含有する医薬品 |
IL138297A0 (en) | 1998-03-27 | 2001-10-31 | Genentech Inc | Antagonists for treatment of cd11/cd18 adhesion receptor mediated disorders |
JP2000072766A (ja) * | 1998-08-27 | 2000-03-07 | Dai Ichi Seiyaku Co Ltd | ベンゾピラン誘導体 |
WO2000015604A1 (fr) * | 1998-09-11 | 2000-03-23 | Kyorin Pharmaceutical Co., Ltd. | Derives de diesters maloniques et leur procede d'obtention |
US6331640B1 (en) | 1998-10-13 | 2001-12-18 | Hoffmann-La Roche Inc. | Diaminopropionic acid derivatives |
AU774054B2 (en) * | 1999-04-02 | 2004-06-17 | Icos Corporation | Inhibitors of LFA-1 binding to ICAMs and uses thereof |
EP1046651A1 (fr) * | 1999-04-19 | 2000-10-25 | Koninklijke Universiteit Nijmegen | Composition et méthode pour moduler l'interaction des cellules dendritiques et les cellules T |
-
2001
- 2001-01-05 US US09/754,888 patent/US6515124B2/en not_active Expired - Fee Related
- 2001-02-01 AU AU2001230227A patent/AU2001230227B2/en not_active Ceased
- 2001-02-01 EP EP01902380A patent/EP1261579A1/fr not_active Withdrawn
- 2001-02-01 KR KR1020027010215A patent/KR100710958B1/ko not_active IP Right Cessation
- 2001-02-01 MX MXPA02007461A patent/MXPA02007461A/es active IP Right Grant
- 2001-02-01 WO PCT/EP2001/001078 patent/WO2001058853A1/fr active Application Filing
- 2001-02-01 BR BR0108240-0A patent/BR0108240A/pt not_active IP Right Cessation
- 2001-02-01 CA CA002397993A patent/CA2397993A1/fr not_active Abandoned
- 2001-02-01 JP JP2001558405A patent/JP2003522751A/ja active Pending
- 2001-02-01 AU AU3022701A patent/AU3022701A/xx active Pending
- 2001-02-01 CN CNB018048218A patent/CN1257886C/zh not_active Expired - Fee Related
-
2002
- 2002-07-17 ZA ZA200205706A patent/ZA200205706B/en unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5559109A (en) | 1989-04-28 | 1996-09-24 | Sankko Company, Limited | Method of treating a PAF-mediated pathology or for treating or preventing psoriasis, nephritis, asthma or shock by administering a PAF antagonist |
EP0410742A1 (fr) * | 1989-07-26 | 1991-01-30 | Allergan, Inc. | Composés phényléthényliques ayant une activité semblable aux rétinoides |
US5457124A (en) | 1993-12-07 | 1995-10-10 | Hoffmann-La Roche Inc. | Carboxylic acid Leukotriene B4 antagonists |
Also Published As
Publication number | Publication date |
---|---|
CA2397993A1 (fr) | 2001-08-16 |
MXPA02007461A (es) | 2002-12-13 |
EP1261579A1 (fr) | 2002-12-04 |
ZA200205706B (en) | 2003-10-17 |
KR20020073206A (ko) | 2002-09-19 |
CN1398252A (zh) | 2003-02-19 |
AU2001230227B2 (en) | 2006-03-16 |
BR0108240A (pt) | 2002-10-29 |
JP2003522751A (ja) | 2003-07-29 |
US6515124B2 (en) | 2003-02-04 |
WO2001058853A1 (fr) | 2001-08-16 |
AU3022701A (en) | 2001-08-20 |
CN1257886C (zh) | 2006-05-31 |
US20020161237A1 (en) | 2002-10-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100710958B1 (ko) | 데하이드로 아미노산 | |
KR910004430B1 (ko) | 5-피리딜-1,3-티아졸 유도체의 제조방법 | |
KR100269756B1 (ko) | 피페리디닐티아시클릭유도체(Piperidinyl Thiacyclic Derivatives) | |
JPH06500557A (ja) | ロイコトリエン生合成を阻害するインドール誘導体 | |
KR900003490B1 (ko) | 쯔비터이온성 비사이클릭 화합물 및 이의 염, 용매화물, 수화물 및 에스테르, 이의 제조방법 및 이를 함유하는 약제학적 조성물 | |
AU2001230227A1 (en) | Dehydroamino acids | |
JP2001503037A (ja) | マトリクス金属プロテナイーゼおよびtaceに対する阻害薬としてのオルト―スルホンアミドヘテロアリールヒドロキサム酸の製造および使用 | |
JPH11513382A (ja) | 5員複素環化合物、これらの化合物を含む医薬品、それらの使用及びそれらの調製方法 | |
KR100886854B1 (ko) | N-페닐아릴설폰아미드 화합물, 이 화합물을 유효성분으로서 함유하는 약제, 이 화합물의 합성 중간체 및이의 제조 방법 | |
JPH10500425A (ja) | 薬学的なジケトピペラジン化合物 | |
JPH06505979A (ja) | ベンゾフラン誘導体 | |
JPH0812649A (ja) | 新規な(チア)シクロアルキル〔b〕インドール類、それらの製造法及びそれらを含む医薬組成物 | |
TW200305396A (en) | Cartilage extracellular matrix degradation | |
KR900006118B1 (ko) | 4-퀴놀론 유도체의 제법 | |
US4258047A (en) | Pyrazole derivatives, pharmaceutical formulations thereof | |
WO2000007985A1 (fr) | Nouveaux derives d'uree renfermant des heterocycles aromatiques azotes | |
WO2001085724A1 (fr) | Ligands (iii) des recepteurs de la cholecystokinine et de la gastrine | |
JPH07278148A (ja) | イミダゾピラゾール誘導体 | |
JP2002053557A (ja) | アポリポ蛋白a−i産生促進薬 | |
US4428962A (en) | Indoles in treatment of peptic ulcers | |
US4859679A (en) | Antiulcer (alkyldithio) quinoline derivatives | |
JPS60105672A (ja) | 胃抗分泌剤としてのチアトリアジンジオキサイド類 | |
JPH0841027A (ja) | 3−ヘテロ脂肪−及び3−ヘテロ(アリール)脂肪−2(1h)−キノロン誘導体 | |
US7105558B2 (en) | Gastrin and cholecystokinin receptor lignads (iv) | |
JPH09509957A (ja) | 免疫調節剤としてのキノリン誘導体 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
GRNT | Written decision to grant | ||
LAPS | Lapse due to unpaid annual fee |